Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA.

Authors: Li, Jingxia; Ma, Cuiling; Huang, Yi; Luo, Jia; Huang, Chuanshu

Published In Oncogene, (2003 Jan 16)

Abstract: The transcription factor activator protein-1 (AP-1) has been implicated in a large variety of biological processes including cell differentiation, proliferation, apoptosis and oncogenic transformation. It is thought that the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity is because of the activation of the PKC/MAPK/AP-1 pathway, although the detailed molecular mechanism has not been fully characterized. The tyrosine kinases of epidermal growth factor receptor (EGFR) lie at the head of a complex of signal transduction cascade that modulates cell proliferation, survival, adhesion, migration and differentiation. Currently, little is known about whether EGFR or its tyrosine kinase is necessary for TPA-induced AP-1 activation. In the present study, we investigated this issue using a well-characterized mouse fibroblast B82 cell line, which is devoid of the EGFR, and its stable transfectants with either wild-type EGFR (B82L) or tyrosine kinase-deficient EGFR (mutation at Lys-721) (B82M721). We demonstrated that the TPA or epidermal growth factor (EGF) induced AP-1 activation in the B82L cells that express wild-type EGFR, but not in the B82 cell, whereas autophosphorylation at tyrosine(1173) of EGFR in B82L cells was only induced by EGF, but not TPA. The expression of tyrosine kinase-deficient EGFR (mutation at Lys-721) (B82M721) resulted in deficiency of AP-1 induction in cellular response to EGF, while TPA treatment led to fully AP-1 activation. Furthermore, the mutation at Lys-721 of EGFR resulted in impairing of EGFR autophosphorylation at tyrosine(1173) induced by EGF. Based on these results, we conclude that TPA-induced AP-1 activation requires the basal level-EGFR protein, but not EGFR tyrosine kinase and EGFR autophosphorylation at tyrosine(1173), whereas both EGFR tyrosine kinase and EGFR autophosphorylation at Y(1173) play a critical role in EGF-induced AP-1 activation.

PubMed ID: 12527890 Exiting the NIEHS site

MeSH Terms: Animals; Cells, Cultured; Enzyme Activation/drug effects; Epidermal Growth Factor/metabolism; Epidermal Growth Factor/pharmacology*; Fibroblasts; Humans; Lysine/genetics; Mice; Mitogen-Activated Protein Kinases/drug effects; Mitogen-Activated Protein Kinases/metabolism; Phosphorylation; Point Mutation; Receptor, Epidermal Growth Factor/genetics; Receptor, Epidermal Growth Factor/metabolism*; Tetradecanoylphorbol Acetate/pharmacology*; Transcription Factor AP-1/drug effects; Transcription Factor AP-1/genetics*; Transcription Factor AP-1/metabolism; Transcriptional Activation/drug effects*; Transfection; Tyrosine/metabolism

Back
to Top